TY - JOUR T1 - Loss of IL-6 promotes alveolar progenitor cells and lung growth in newborn mice exposed to mechanical ventilation JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.5243 VL - 56 IS - suppl 64 SP - 5243 AU - Jasmine Mohr AU - Hanan Kesler AU - Dharmesh Hirani AU - Margarete Odenthal AU - Jörg Dötsch AU - Miguel A. Alejandre Alcazar Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/5243.abstract N2 - Rationale: Mechanical ventilation (MV) of premature infants often leads to Bronchopulmonary dysplasia (BPD), which is characterized by an impaired alveolarization and regeneration. Since prior studies from our group showed that activation of inflammatory IL-6 signaling is a key mechanism of BPD, we hypothesized that IL-6 deficiency protects from MV-induced lung growth arrest.Methods: IL‑6‑deficient mice (IL‑6-/-) mice and wildtype controls (WT) were ventilated (21% O2) for 8 h at postnatal day 5 (P5).Results: 1) MV induced a 10-fold increase of IL-6 expression and a markedly activated lung Stat3 signaling of WT mice. Activation of pulmonary IL-6 signaling was related to previously shown lung growth arrest. The number of CD68+ cells was significantly higher in ventilated WT mice compared to controls. 2) To investigate the functional role of IL-6 we analyzed ventilated and non-ventilated IL-6-/- mice. The significant increase in the number of macrophages (CD68+ cells) was not attenuated in lungs of ventilated IL-6-/- pups compared to IL-6-/- controls. However, IL-6-/- pups were protected from arrested alveolar formation after MV. These findings were related to a greater content of elastic fibers and collagen in IL 6-/- mice than in WT mice. Moreover, the number of alveolar epithelial cells type II (SPC+ cells) was increased in IL 6-/- mice in comparison to WT mice.Conclusion: Our data demonstrate an activation of pulmonary IL-6 signaling in MV-induced lung growth arrest. Loss of IL-6, however, promotes lung growth and survival of alveolar progenitor cells in ventilated newborn mice, offering thereby a novel potential target to treat preterm infants with BPD.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 5243.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -